=food =biology =chemistry =drugs
Alcoholic drinks are popular in
most of the world. Excessive consumption of them is also a major public
health problem. Bans have been attempted, sometimes
successfully,
sometimes
unsuccessfully, but some people argue that alcohol plays a necessary
role in social interactions.
Alcoholic drinks contain ethanol, which
is metabolized to acetaldehyde, which is metabolized to acetate. In cells,
ethanol is mostly unreactive but can bind to receptors. Acetaldehyde
reacts with lots of stuff, mostly reversibly but sometimes irreversibly.
Small amounts of acetate are essentially irrelevant, mostly providing
calories.
Acetaldehyde can inactivate enzymes by causing
crosslinking. Large amounts of it are generally bad. We can separate out the
effects of ethanol itself and acetaldehyde by looking at people who
metabolize acetaldehyde slowly.
About 50% of people of Northeast Asian descent have a dominant mutation in their acetaldehyde dehydrogenase gene, making this enzyme less effective, which causes the alcohol flush reaction, also known as Asian flush syndrome. A similar mutation is found in about 5–10% of blond-haired blue-eyed people of Northern European descent. In these people, acetaldehyde accumulates after drinking alcohol, leading to symptoms of acetaldehyde poisoning, including the characteristic flushing of the skin and increased heart and respiration rates. Other symptoms can include severe abdominal and urinary tract cramping, hot and cold flashes, profuse sweating, and profound malaise. Individuals with deficient acetaldehyde dehydrogenase activity are far less likely to become alcoholics, but seem to be at a greater risk of liver damage, alcohol-induced asthma, and contracting cancers of the oro-pharynx and esophagus due to acetaldehyde overexposure.
alternatives to ethanol
Ethanol is what's in
drinks because it's produced naturally by a common type of fermentation, it
prevents growth of most harmful microbes, and the yeast produced has some
nutritional value. But our modern industrial civilization is no longer bound
by such prosaic concerns. Can we do better?
ether
Studies, including that of an ether addict in 2003, have shown that ether causes dependence; however, the only symptom observed was a will to consume more ether. No withdrawal symptoms were prevalent.
—
Wikipedia
Diethyl
ether has the same direct effect as ethanol, but mostly isn't metabolized in
the body. Some of it gets metabolized (by a monooxygenase) by oxidation to
(ethanol + acetaldehyde), but more of it gets exhaled. Thus, it's similar to
what ethanol without acetaldehyde production would be like.
Diethyl
ether isn't expensive to make, and there's lots of knowledge about its
effects because it was widely consumed in the past. But it does have some
problems:
- It's volatile and has a strong smell, so it's obnoxious to
other people.
- It has fairly low water solubility, ~6%.
- Above 2% in
air, it's inflammable.
-
Pure diethyl ether exposed to oxygen can slowly form explosive peroxides.
- It's already been banned most places, and unbanning things might be harder
than not banning them.
butanol
At sub-lethal doses, 1-butanol acts as a depressant of the central nervous system, similar to ethanol: one study in rats indicated that the intoxicating potency of 1-butanol is about 6 times higher than that of ethanol, possibly because of its slower transformation by alcohol dehydrogenase.
— Wikipedia
Some butanol
occurs naturally in fermented products. Yeasts could be engineered to
produce mostly butanol instead of ethanol, but the maximum practical
concentration from fermentation is low, ~1%. If it's 6x as effective as
ethanol, then 1% would be enough for drinks. It would then provide a similar
effect to ethanol with less aldehyde production.
Its boiling point is
118C, and its water solubility is 7%, so it wouldn't evaporate much. The
odor is OK, like fruity alcohol, but it's detectable at much lower levels
than ethanol.
Apparently, the odor is less pleasant at higher concentrations, and
hedonically neutral at 300 ppm.
Some naturally occuring microbes produce butanol
together with
acetone.
The acetone could be distilled out relatively easily.
Here's an
EPA summary of 1-butanol rat
studies.
In rats, high doses can cause neurotoxicity and fetal problems. Comparing to
mass of ethanol in beer relative to human weight, no problems were found at
0.6 beers/day but some were found at 1.5 beers/day. Considering that
1-butanol has ~6x the apparent intoxicating effect of ethanol in rats, that
makes sense if those effects come from the same mechanism as the
psychoactive effects of alcohol. However, it's not clear what the rate of
(butanal -> butyrate) is in humans compared to (acetaldehyde -> acetate),
and if it's proportionately slower, then butanol might not be significantly
less problematic than ethanol.
2-methyl-2-butanol
Does
this have similar effects to ethanol? Yes, but it's stronger, and some
people have been (illegally)
using it recreationally.
Since this is a tertiary alcohol (with
the oxygen bonded to a carbon with 3 carbons on it) it can't be metabolized
by dehydrogenation to an aldehyde, which is one way to avoid aldehyde
production. However, that means it lasts too long, leaving people
intoxicated for ~2 days. Also, the smell/taste is somewhat bad.
It's
worth noting that tertiary alcohols produce the same effect too despite
steric issues being plausible.
ethoxyethanol &
butoxyethanol
You might think these are safe because they're used in
eg some paint solvents, but no, they're somewhat toxic. I wish companies
would stop using them in consumer products.
cyclic ethers
We can't
use longer hydrocarbons than diethyl ether or butanol because solubility in
water gets too low, so how about cyclic ethers?
Would cyclic ethers
have the same effect? I'm pretty sure they would. If butanol is stronger
than ethanol, and diethyl ether also works, then the mechanism must involve
molecules fitting inside a protein hydrophobic pocket with a carboxylic acid
group inside it that hydrogen bonds to an ether or alcohol. The effect then
probably comes from protein conformational changes from that type of
hydrophobic pocket being stabilized. Cyclic ethers would be more
conformationally restricted than diethyl ether, yes, but I doubt that would
matter here.
Tetrahydrofuran is a 5-member ring, less volatile than
diethyl ether and miscible with water, but it's toxic, presumably because it
can be metabolized to 1,4 dialdehyde which can react irreversibly in a
Paal–Knorr reaction. For the same reasons it's miscible with water, high
concentrations also disrupt various biological membranes by acting as a
surfactant. It's also somewhat expensive to make, and very flammable, and it
has a tendency to form peroxides.
oxane
Oxane is a
6-member ring. 8% solubility in water and a 88 C boiling point are high
enough. Like how pentanediol is much safer than butanediol, oxane
metabolites are safer than tetrahydrofuran metabolites. The odor is "pungent sweet
ethereal".
As it's a bigger molecule than tetrahydrofuran, and pentanediol costs more
than butanediol, you might expect this to be more expensive to make, but
it's actually cheaper, with 2 practical routes:
route 1:
propene +
formaldehyde
-> (dihydropyran + butadiene + butanal) in a Prins +
Diels-Alder reaction using solid acid catalyst
-> dihydropyran
hydrogenation
The inputs are very cheap, and those side products are
more valuable than the inputs.
route 2:
furfural
-> hydrogenation
to tetrahydrofurfuryl alcohol
-> rearrangement on Al2O3 to dihydropyran
-> dihydropyran hydrogenation
Furfural is made from biomass, so
it's renewable, which I guess is considered good?
I don't want to be
like a high school chemistry teacher handling liquid mercury with their bare
hands in a classroom to show how it's not absorbed through the skin and all
those people afraid of it are just dumb and yes that's a thing that
happened. Even asking my dentist to use articaine instead of their usual
choice makes me worry I'm overlooking something, which is just silly. But
I'm quite confident that pure oxane is safer for humans than ethanol, so I
think people should be able to have some high-oxane entertainment if they
want. My main concern is that it could last too long; it should be cleared
faster than 2-methyl-2-butanol, but because it's less volatile and more
soluble than diethyl ether, it wouldn't be exhaled as quickly.
regulations
I think it
makes sense for some country with a high rate of alcohol flush reaction to
legalize using 1-butanol or oxane as a substitute for ethanol in drinks
served at bars and restaurants. If that works out well, people could go from
there. However, I'm not sure what would lead to a country doing
that...hmm...isn't it a shame that some Japanese salarymen and OLs can't be
socially pressured by their bosses into consuming psychoactive substances at
company drinking parties merely because they have an adverse reaction?
Clearly, this is a societal problem that demands rectification, and if it
can't be fixed socially it
should be fixed chemically.
Of the above compounds, the one closest
to being legal as an alternative to ethanol is definitely butanol. It's
allowed as a flavoring in the US; my understanding is, there's no specific
limit but usage must be at the lowest level that accomplishes the purpose
(of flavoring).
To me, oxane seems like the best ethanol replacement,
followed by butanol. As for oxane regulations, it hasn't really been
considered by governments at all.
Really, ethanol in drinks is only
allowed because it was used historically; I doubt it would be allowed if it
was new. If you look at how drugs are handled...in the US, for example,
methylphenidate
is obligatory for some kids while
ethylphenidate is illegal,
and they're basically the same but ethylphenidate is probably slightly
better.